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Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt. Public health department ,.Director of ghubera tuberculosis team .First health cluster , Riaydh, Ministry of health Saudia Arabia These Authors contributed Equally Correspondence, Mahmoud Elkazza, Email; mahmoudramadan2051@yahoo.com and Amr Ahmed ,drmedahmed@gmail.com Abstract A common symptoms of COVID-19 is a change or disorder in hormonal balance and olfactory function which may persist after recovery such persistent COVID-19–related anosmia and hormonal imbalance . Hormonal problems are being seen in patients who have recovered from Covid-19 infection. Moreover, anosmiais a well-tolerated symptomof COVID-19, but their etiology isn't understood. The same condition were seen in Kallmann syndrome,the sense of smell is either completely absent (anosmia) or diminished (hyposmia). Furthermore, hypogonadotropic hypogonadism is seen as common symptoms of Kallmann syndrome,. In this review , we are attempting to elucidate the direct mechanism of hormonal imbalance, anosmia and long-term neurological complications which are caused by COVID-19 infection and persist after recovery Therefore, we suggest attestable hypothesis with confirming docking results that COVID-19 directly binds to STRA6receptor which is a membrane receptor that mediates cellular uptake ofvitamin Aor plasmaretinolbinding protein (RBP) leading to its downregulation and retinoic acid deficiency. Retinoic acid plays critical physiological roles insynaptic plasticity, learning and memory, hormone production, immunity and adult neurogenesis. Retinoic acid-mediated pathways of growth regulation (nuclear receptor mediated) and vision (G protein-coupled receptor mediated). A recent study strongly suggests that RA is an important regulator of the GnRH neurons. Retinoic acid induces expression of G protein-coupled receptors that are used by Gonadotropin-releasing hormone (GnRH). Therefore, STRA6 downregulation and retinoic acid deficiency in COVID-19 patients may lead to disruption of Gonadotropin-releasing hormone (GnRH) signaling pathway in olfactory neurons and result in hormonal in balance , anosmia and hypogonadism. In addition, we suggest that SARS-CoV-2 uses the STRA6 receptors as the nervous route for invading brain. Furthermore, we report effective treatment ofanosmiaby aerosolized retinoic acid therapy which is expected to act thorough multimechanisms, it worth mentioning that aerosolized all- trans retinoic acid is currently under clinical investigation by the authors (ClinicalTrials.gov Identifier: NCT05002530) |
